title: The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4(+) T cell responses towards IL-4 production.
abstract: BACKGROUND
  Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4(+) Th1 and CD8(+) T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.
  
  
  RESULTS
  Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.
  
  
  CONCLUSIONS
  Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.
authors.affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany. m.lutz@vim.uni-wuerzburg.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Heuer
authors.forename: Anna-Sophie
authors.initials: AS
authors.lastname: Behlich
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Lee
authors.forename: Eliana
authors.initials: E
authors.lastname: Ribechini
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D016753:Interleukin-10; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen